Organic Chemistry Biomolecules

Biochemistry requires a strong understanding of the structure, stereochemistry, and reactivity of organic molecules and functional groups. One common biomolecular group is carbohydrates, which include compounds like D-glucose (which can switch from a five-membered ring to a six-membered one), disaccharides, polysaccharides (starches, cellulose), and sugar-containing biomolecules like RNA and DNA. Amino acids and proteins rely heavily on the chemistry of nitrogen. These molecules can contain side chains with different properties, including polarity, acidity, and isolectric point. Lipids/Fats/Triglycerides are the last major class of biomolecules. These can be unsaturated, saturated, partially hydrogenated, saponified (which relies on the creation of micelles), and even synthesized into biodiesel. Cell membranes rely on lipid bilayers made from phosphoglycerides.

Biomolecules

*These practice questions are only helpful when you work on them offline on a piece of paper and then use the solution steps function to check your answer.

Answer

Biomolecules

Lecture Slides are screen-captured images of important points in the lecture. Students can download and print out these lecture slide images to do practice problems as well as take notes while watching the lecture.

Transcription: Biomolecules

Today, we are going to be talking about biologically interesting organic compounds, or we could call them biomolecules for short.0002

Now, there is a reason that, if you are going to be studying biochemistry, you typically need an entire year of organic chemistry to prepare you for biochemistry; and that is because biochemistry is the study of organic molecules and organic reactions that are going on inside living systems.0008

And so, much of it requires, not only an understanding of the structures of molecules, the stereochemistry, and so on, but also the reactivity of different functional groups.0025

And so, today, we are going to be studying different classes of biologically relevant molecules, some of which you may have already seen a little bit before; but others--we are going to get into a lot more detail.0036

And still, this is all at a level that is not at the biochemistry level; I am not a biochemist, and this is not a biochemistry course; but it is going to give you an introduction from an organic chemist's point of view, in terms of what the significant functional groups are, and seeing if we can understand a little bit of how these molecules come together and what behavior they might have in actual systems.0050

Carbohydrates is another word...an example of carbohydrates are sugars; and so, we know of sugars; carbohydrates are one of the things that we can eat and digest as part of our diet, in addition to proteins and fats.0072

And so, in fact, we are going to be talking about all three of those things today; so obviously, all of those components are significant when it comes to the metabolism of those compounds and converting those into energy for our bodies' use.0090

This is a general structure of a sugar; there are lots of different sugars we can have; this one is described as a hexose, because it has 6 carbons.0102

And it is also described as just a monosaccharide; we are going to see that these can form chains--they can link together to form a disaccharide, if we have two sugar units; and it could actually make long polymer chains--we call those polysaccharides.0113

This is the structure of D-glucose; that is the sugar we know as blood sugar.0126

If you are a diabetic, you have problems with insulin production and maintenance of a proper sugar level; it is the glucose in your blood that you are testing, any time you test your blood, and that you are trying to monitor and keep at an appropriate level.0131

And so, glucose is a hexose--we see that up here; it has an aldehyde functional group, and then it is a polyol--it has several hydroxyl groups.0150

And this isomer that I have shown here is D-glucose, and if you imagine the mirror image of this, you would have the exact same relative relationship; it would just be the mirror image.0160

Nature typically prepares only a single enantiomer of any chiral molecule, and so sugars are an example of that.0175

The ones that are naturally occurring are described as D-sugars, and the way we identify a D-sugar is: if we draw a Fischer projection (like this, where the most highly oxidized carbon is up top, and we draw all our chiral centers going down), if we look at the very last chiral center, if this OH is on the right, as shown, then that is a naturally occurring sugar; we are going to call it a D-sugar.0185

Now, that D--the opposite...the enantiomer...if we were to draw the mirror image of this, that would put all of the OH's in the opposite position, including this last one on the left; that one would be described as the L-sugar.0211

That is different from the lowercase d and l we have seen for stereochemistry: remember, when we talked about optical activity, we described the optical rotation.0230

It could be a + or a -α, and those that were +α we described as dextrorotatory, and the -α is levorotatory.0239

That little d and little l just depend on the molecular structure; we have to measure those; we can't predict those; and those have nothing to do with the designation of d and l that we are going to use for sugars and amino acids.0248

Make sure that you keep in note--"Not the same as d and l"--little d and little l.0261

This is D-glucose, and D-glucose can exist in the straight-chain conformation, but actually, in solution (in blood and at that pH), it actually forms a ring; it prefers to exist in a cyclic form.0271

And we are going to form a 6-membered ring (remember, 6-membered rings are very easy to form, because they have no ring strain).0290

And so, the way it can form a ring is...what we have here is a carbonyl carbon; the reactivity of a carbonyl is going to be electrophilic--there is a partial positive on that carbon to make it electrophilic.0296

And we have, with all of these OH's, a variety of nucleophiles; so if we look, 1, 2, 3, 4, 5, 6 atoms away we have a potential nucleophile.0308

I'm actually going to take this OH on the last chiral center; and if we bring that up and form a ring, we are going to form a 6-membered ring.0324

Now, we know that 6-membered rings prefer to take the chair conformation, so we are going to draw our chair that way.0333

And, if we always draw our chair with this general shape--so we start with a zigzag up and go down--and we always put the oxygen in this top right corner; if we always draw our sugar, our 6-membered ring, in the same way, then it is going to be very easy to draw a glucose, because all of the OH groups are in equatorial positions; so it is a very stable molecule.0340

And if we number our carbons, this is the carbon that got attacked--that is carbon 1--and this is 2 (it had an OH); 3 had an OH; 4 had an OH; and then, 5 has this oxygen, and then it has, also, a CH2OH.0372

This is carbon 5, and up here, we have a CH2OH; so all of the substituents in glucose are equatorial--that means they are pretty easy to identify, or draw if you need to.0388

Now, let's think about on carbon 1...carbon 1 used to be the carbonyl; it is now a single bond oxygen, which is going to get protonated, and we are going to have an OH here.0401

And I am going to draw this...when you think about the stereochemistry of this OH, this is forming a new chiral center; so it's not fixed--you can either draw the OH in the equatorial position, or you could draw it in the axial position.0409

I'm going to draw it as a wiggle line, and that means we can get a mixed stereochemistry; we'll look at that stereochemistry in just a bit, on the next slide.0422

And another thing I want to point out about this cyclic form of the sugar is that this carbon--this is a very special carbon; it is described as the anomeric carbon.0434

And that is the carbon that used to be the carbonyl; notice, the carbonyl has two bonds to oxygen.0447

Well, even in the cyclic form, it still has two bonds to oxygen: here is one bond, and here is the other bond--2 bonds to oxygen.0453

That is going to make it very special and unique, and it is going to be something we can pick out of any cyclic sugar--this anomeric carbon.0463

There is special reactivity that is associated with this anomeric carbon we are going to be seeing.0473

And, if we ever need to correlate that with the straight-chain form, we know that that anomeric carbon that is numbered 1 here corresponds to the carbonyl carbon.0477

That is either an aldehyde or some sugar that is a ketone; there are aldoses and ketoses, depending on what the carbonyl is like; but glucose has an aldehyde here.0487

OK, so let's take a look at where the OH is: we have different names for the sugars--different stereochemistry.0496

These are the 6-membered rings of glucose; if the OH is on the anomeric carbon--so I can find that anomeric carbon...0504

Now again, just because I usually draw it in the same general reference--it is the furthest-right carbon, but no matter how it is drawn, I see that this is the carbon with two C-O bonds.0512

And if the OH is pointing in the down position, we describe that as the α stereoisomer; so that means the anomeric OH is down, meaning it is in axial position.0527

And, if the OH is pointing up, we call that β: the anomeric is pointing up, and this is in the equatorial position.0549

OK, so when it's in a 6-membered ring, we no longer just call it glucose: we call it glucopyranose; a pyranose means it's a 6-membered ring--like pyran is a structure with a 6-membered ring.0568

The full name for this molecule would be α-D-glucopyranose; and this is β-D-glucopyranose; and both of these exist--both of them are formed--when glucose cyclizes, and both of these exist in blood.0586

Now, when it's a cyclic form, how can we tell whether it's a D-sugar or an L-sugar (the naturally-occurring sugar)?0602

Well, for the 6-membered ring, we are going to have--this is the last chiral carbon, the last chiral center; that is the one that can show us whether we are looking at a D-sugar or an L-sugar.0608

And so, again, when we always draw this same cyclo chair backbone of the 6-membered ring (it's not cyclohexane, because we have an oxygen in there), when we always have that same backbone, then having the CH2OH group up--that tells us that it is the D, the naturally-occurring.0620

Now, we usually don't see any of the L-sugars, but if you ever need to distinguish between them, or if that is part of the assignment (to pick out the L-sugar), this is where we would look.0647

The last carbon, the CH2OH, is up, so that means it is the D enantiomer that we are looking at.0655

Now, glucose can also exist in a 5-membered ring, instead of a 6-membered ring: so here is 1, 2, 3, 4; if we stop at this oxygen, that is also a nucleophile that is in a proper position to attack the electrophile.0665

And remember, 5-membered rings are reasonable to form, just like 6-membered rings; and so, what would that look like?--the oxygen attacks the carbonyl, and then we would form a 5-membered ring with an oxygen in there.0683

And if we keep this carbon as carbon 1 on the right...now again, that carbon will have an OH, but it is of a mixed stereochemistry, so that OH can be pointing up or down.0699

And then, we have the OH's; I don't have my stereochemistry right--I didn't draw these down.0711

We draw this kind of like a 5-membered ring that is pointing out towards us; we are looking at it from the side, so each of these positions, you could draw the position as up or down.0719

So, if we tilt this molecule on its side, we see this first OH is down, and the second OH is up, and the next OH we rotated around, and so I think it's pointing up here.0733

I think this is the structure; I have it written out on the next slide, so we will see for sure.0748

So, these are the two examples; and I think I just about had it right; so the place where we can have some variability in the structure and still have it be glucose (these are still glucose molecules)--now we call it glucofuranose, like a furan ring is a 5-membered ring.0757

And, if we look at that anomeric carbon--anomeric used to be the carbonyl, and now has two separate bonds to oxygen--once again, we use the same terminology, the α position, because our OH on the anomeric carbon is down.0781

OK, so we don't use the words axial and equatorial--that makes sense here, because it is not a 6-membered ring; but we just look for up or down to describe that.0808

And that up or down--that α and the β--is related to the fact that this is the D-sugar; so going back to that 6-membered ring, assuming it's the D-sugar and that the CH2OH is up, then α is also up.0817

So, it is actually describing its relationship to that CH2OH; so the α and β won't have the same connotation otherwise.0830

OK, now let's see if we can try a mechanism, putting our organic chemistry hats on.0844

Let's see if we can come up with a mechanism to show how we can maybe go from a 6-membered ring to a 5-membered ring.0848

Now, what I did was: I simplified this problem by taking out all of the dashes and wedges; so I haven't shown the stereochemistry of all of these chirality centers.0854

Glucose has a certain stereochemistry for each of its chiral centers; if you change any of those locations of the OH groups, it is no longer glucose--it's maybe galactose or raffinose or some other sugar.0864

The first thing you want to do is...remember, these are coming from the same sugar, the same acyclic sugar; so let's try and identify the carbon chain that is going to be common to both.0891

Now, remember, they both started with a carbonyl; that carbonyl carbon had 2 C-O bonds; that carbon, even in the cyclic form, still has two C-O bonds; so the key here is: let's identify the anomeric carbon, and that is going to help us track the rest of the carbon chain.0900

On this first structure, we look around: every carbon has just one bond, one bond, one bond, and then we find that this is the carbon that has 2 C-O bonds; so let's call that carbon #1, and we'll label it "anomeric carbon," just so we are clear on that.0916

And then, let's find that over here: one carbon, one carbon, one carbon; the carbon-oxygen bond is what I'm counting--there is our carbon that has 2 C-O bonds.0936

What is great about that--we could label that 1, and then we can follow our carbon chain, right?--this is not our carbon chain; this is our carbon chain: 1, 2, 3, 4, 5, 6; and over here, we have 1, 2, 3, 4, 5, 6.0952

We know where all our carbons are as we track them; and what is going to be happening here is: we are going to be taking the cyclic structure, and we are going to be opening up the ring to go back to an acyclic structure, and then reclosing it, using a different oxygen, to form a 5-membered ring instead of a 6-membered ring.0970

How do we open up that ring--what is the bond that we are breaking?--it is this anomeric carbon that needs to go back to being a carbonyl.0990

This is the bond that we are going to be breaking--this oxygen on the carbon chain is going to go back to being just an OH group.0998

What does our mechanism look like?--well, let's assume we have an acid catalyst; so our first step must be to protonate somewhere.1007

I can protonate any of these oxygens--any of these oxygens can and will be protonated.1015

But, if I protonate the oxygen that I want to leave, when that one gets protonated, let's take a look at the structure that we end up with.1020

OK, lots of OH's; you can see why ignoring our stereochemistry helps us out a little bit.1034

And now, we have protonated; OK, now, what did we make?--by protonating this oxygen, we have made an intermediate that is tetrahedral.1042

There is a hydrogen here: it has 4 groups--2 groups have lone pairs; one of the groups has a charge; does this intermediate look familiar?1056

A CTI is something where bells and whistles (ding, ding, ding!) went off, because we said, "Hey, I know that structure!--this is something that can be unstable."1070

And, in fact, what can a CTI do?--it can collapse, and that means the leaving group leaves, but the leaving group leaves with assistance from the other group; so this lone pair kicks down, and this bond breaks, and that group gets kicked out.1077

And what we end up with, now, is...and there was a hydrogen here; you can add that in, because usually we draw our aldehydes with a hydrogen there...so this, now, has a carbonyl; that is carbon 1.1094

And then, we can number our carbons again: this is 1, 2, 3, 4, 5, 6; keep track of them--that is good.1111

And then, I don't know where the stereochemistry is; so we could just draw them--it doesn't really matter.1120

But carbon 2 has an OH; carbon 3 has an OH; carbon 4 has an OH; carbon 5--what does carbon 5 have?--it now also has an OH, and then a CH2OH.1127

OK, now I have drawn a Fischer projection, which now implies a stereochemistry; but let's just make a little note that we can ignore the stereochemistry; there is nothing special--I just wanted to draw this out of the straight chain.1143

We have a protonated carbonyl that looks like a great electrophile, and if we go 1, 2, 3, 4, 5, then if this oxygen is our nucleophile, if this attacks the carbonyl, then that is going to close up and form a 5-membered ring.1163

Let's take a look at where that brings us: I'll draw it with this orientation.1183

I know I formed a 5-membered ring with an oxygen, so all I have to do is draw that tetrahydrofuran ring.1189

And let's relate it to the structure that we are already given; so let's call this carbon #1; #1 has an OH (σ bond OH now); carbon 2 has an OH; carbon 3 has an OH; carbon 4 has this oxygen, which was an OH; it is still an OH, so that looks like an O+; and then, that oxygen just formed this bond to 1 and formed this bond to 1.1198

OK, so you can see that this was the new bond that was formed; we broke one bond, and then we formed a different bond.1232

And what else is on carbon 4?--carbon 4 has a carbon with an OH, and then CH2OH.1238

OK, so we have formed our bond, but we have one more step to do, because we attacked with a neutral alcohol; and so, this is now positively charged OH, and so, we just need to deprotonate as our final step.1255

So, just like we used HA in the first step, we get that HA back in our last step; so this is just catalytic--all we need is a catalytic amount of HA to get this mechanism going; and then we are done.1269

OK, so looking at sugars as organic molecules--as aldehydes reacting with alcohols--we know how to do carbonyl chemistry; we can do those mechanisms.1282

Now, it turns out that sugars are actually building blocks that nature uses; they are also building blocks that synthetic chemists can use.1295

They represent wonderful starting materials, because they are provided by nature with chiral centers intact.1305

So, if you want to generate a chiral target molecule or a chiral drug target, let's say, a sugar is a great starting point, because you already have a certain number of chiral centers that are already set for you.1312

OK, so let's look at some of the reactions that sugars can undergo; and this is going to set the stage for some of the reactions we'll see down the line.1325

OK, so one thing we can do with glucose or any other sugar is: we can form an acetal.1332

The way we form an acetal is: we react the sugar with an alcohol and some acid catalyst.1338

OK, now, notice: when you do this reaction, the only product we get--the only methoxy group that gets added in--is at the...which carbon?--at the anomeric carbon.1347

So, it is the anomeric carbon that has that special reactivity; none of these other alcohols react.1359

These are just plain old alcohols, but this is not a plain old alcohol; this OH is on the same carbon as an O-R, and we have a name for a functional group when we have an OH and an O-R: we call that a hemiacetal--the word that is right there--a hemiacetal.1364

So, sugars in the cyclic form are hemiacetals; normally we wouldn't form a hemiacetal, because they are not very stable, but in the cyclic form they are, and cyclic sugars--this is the one example where we are going to see them.1384

OK, so what happens with a hemiacetal when you treat it with some more alcohol and acid--what is going to form is: we are going to replace this OH with another O-R.1397

And what do we call it when a carbon has 2 O-R groups on it, 2 alkoxy groups on it?--we call it an acetal.1411

A cyclic sugar is a hemiacetal; a reaction with an alcohol converts it to an acetal.1419

Now, this bond that we make to the anomeric carbon--this is known as a glycosidic...it is called a glycosidic bond.1427

OK, so methyl, because we added on a methyl group here; α--what does α tell us?--it tells us the stereochemistry at the anomeric carbon, and here we have the oxygen that is pointing down--that is the α stereochemistry.1442

D means it is the naturally occurring sugar, and I could see that because the CH2OH is pointing up, like we know for the glucose.1459

Gluco, because we are dealing with glucose; I can tell that because all of these groups are in the equatorial position.1468

And then , the glucoside means that I have formed this glycosidic bond; so that means there is something now attached at that anomeric carbon.1474

And this is the bond that we can form, that sugars can form, and that is a way of linking one sugar molecule to another sugar molecule.1489

So, if we strip this away--let's say we wanted to do the mechanism for this; again, we are organic chemists, so this is not just magic that happens; this is something we can provide a mechanism for.1497

To do the mechanism, let's just strip away all of this extra stuff, all the functional groups that are not involved in the mechanism, and go down to the bare bones; so this is what we have.1510

Here is the structure of a hemiacetal: cyclic 6-membered ring with...the carbon that has the oxygen has another OH.1518

OK, I don't care about any of the OH's that are just plain alcohols: alcohols don't react with alcohols--there is no reaction there.1529

OK, but here is the hemiacetal with our anomeric carbon, and we are getting a substitution taking place with that anomeric carbon where the OH is getting replaced with an OCH3.1536

OK, what does that do for us--why is that good to protonate?--because now we have a very good leaving group.1575

What would it be if it were to leave?--it would just be a molecule of water; you don't get a more stable leaving group than water.1582

OK, so we just made a good leaving group, and we have a nucleophile; now, how is that going to come in--how is it going to replace?1589

SN1 means the leaving group just leaves--just ordinarily, you get a random carbocation and the leaving group, and the nucleophile comes in.1597

Back side attack can happen: back side attack means that my methanol would kick out the leaving group; but this isn't a very strong nucleophile, so back side attack doesn't look very good.1606

Well, in fact, neither of those mechanisms happens because this is not just an ordinary leaving group on an ordinary carbon; it's a leaving group on the anomeric carbon.1615

So, this is not just a random leaving group; what I have here as an intermediate is a charged tetrahedral intermediate.1623

OK, so when you have a CTI, it is now carbonyl chemistry; this is not an ordinary SN1 or an ordinary SN2; what happens is: the leaving group leaves with assistance from this leaving group.1630

That is why the reaction happens here and not at any of the other OH's that are on the carbon chain.1645

OK, if it was just a plain old SN1 or SN2, you could react anywhere you want; but no, what makes this special is: protonating at this oxygen gives a CTI.1653

And how does the CTI kick out its leaving group?--we use two arrows; it collapses.1663

It collapses; we get a resonance-stabilized carbocation intermediate.1668

OK, so by using two arrows to collapse your CTI...collapse the CTI, and we just kicked out our molecule of water...now we see the carbonyl.1674

We see that this is, in fact, carbonyl chemistry; our anomeric carbon goes back to being a carbonyl.1686

This is now a great electrophile; it is like a protonated carbonyl; and so now, hopefully, you can see how our nucleophile, the methanol, can get involved.1691

The methanol will attack at the carbonyl carbon and break the π bond.1702

So now, this oxygen has its lone pairs back, and how about this oxygen?--it has a methyl, has a hydrogen, one lone pair--so that is now my O+.1711

This is part of the mechanism that is used; go back and review your mechanism formation of an acetal; part of the mechanism--we are kind of looking at the last part of the mechanism, where we have gotten to the hemiacetal, and now we are kicking out that water, and we are bringing in the second molecule of the alcohol.1723

Here we already have one of the O-R groups in place, so we are just adding in the other O-R.1740

OK, and all we have to do is deprotonate, so I can use my A- that I formed in the first step.1745

So again, this is catalytic, just like any acetal formation; catalytic and acid, and we are done.1749

OK, so what is important is that we recognize that the anomeric carbon of a carbohydrate is a special one, and substitutions can occur at that position very readily, because that other oxygen can help forcing out the leaving group.1759

This is the way that we can form sugar chains; if we just bring two sugar units together, we can form a disaccharide, meaning there is a 2-sugar unit.1775

So, if we bring together glucose (that is the blood sugar that we have been working with) and--this one is called fructose (again, both the naturally occurring fructose is...you may have heard of that: that is the sugar that is in fruit, that makes it naturally sweet)...so if we bring these two together, instead of just methanol coming in and replacing...this is the OH that is going to be leaving; there is our leaving group.1785

And who is the nucleophile?--well, we can see that it is the other OH, so actually, one of these is the leaving group or the nucleophile (we can kind of think of it either way--leaving group/nucleophile)--the point is: one of those OH's is getting kicked out, and the other oxygen is coming back in.1811

And they are both happening at the anomeric carbon, and so, that is where we can get our reaction to take place.1829

We lose water in this reaction; we eliminate a molecule of water, so it's a condensation reaction; and we end up with this disaccharide; and when you mix one molecule of glucose with one molecule of fructose, we know this as sucrose.1838

And sucrose is what we use as table sugar; so this is what we take spoonsful and put on our cereal, or in our coffee, or we use in baking: this is the sugar we use in our cooking as a sweetening agent.1856

And so, we took our fruit sugar and blood sugar components to make that.1870

So of course, when we consume this as something in our diet, then this is going to be cleaved, and it is going to yield, again, a molecule of glucose and a molecule of fructose.1874

That is why sucrose--taking in table sugar--has a significant impact on our glucose levels.1886

Now, we can use this same idea and form polysaccharides, meaning we are forming long carbon chains.1894

And so, this first example we will look at is starch; now, starch--there are a couple different versions of this.1902

Amylose is an unbranched version, so we just kind of get a long chain; amylopectin is a highly-branched version; so here we are showing a branched version, because here we have a chain of glucose units, and then it is chained off this way.1910

So, when you take a look at a glucose unit, what has happened is: we have formed a bond to the anomeric carbon (OK, that is always where we are going to be attaching some new nucleophile).1922

And so, here we have attached it to this OH at the far left on the molecule.1934

Now, these glycosidic bonds are described as α-1,4-glycosidic bonds; so we see the α that describes the position of the group that has been attached to the anomeric carbon (it is in the down position).1942

These are all α connections; OK, and it's a 1,4 glycosidic bond--it has gone from carbon 1, the anomeric carbon of one sugar, to 1, 2, 3, 4...the carbon 4 of another sugar.1960

And we can have some cross-branching by introducing, every once in a while...this central glucose unit--this OH, added on to another glucose, and this OH also did; and so now we get a branching point.1981

The nature of these starch molecules is that they are water soluble; look at all the OH's--we have a very polar structure, so it loves water; it is water-soluble.2001

It is digested by animals, so this is the starch that we have in our diets; we can have it in potatoes and rice and bread--those kinds of things that we describe as high-starch items...corn.2012

We also use them as thickening agents, like cornstarch is something you could add to gravy or sauces to make it thicker.2025

And so, we have this polymer structure that can go in there and kind of act as a thickening agent.2032

Now, a different polysaccharide is cellulose; now, notice the structure of cellulose: it kind of has this long, very linear chain; and the difference here is that now we have a β-1,4-glycosidic bond.2038

So, they are still glucose units; they are still being connected at carbon 1 (let's go this way) of one and 1, 2, 3, 4 of the other; notice that every other glucose unit has been flipped over, so we can actually see the structure of it.2053

So, this is carbon 1, 2, 3, 4; so we are connecting at the 4 position and at the 1 position.2075

It is still a 1,4 glycosidic bond, but now each of the anomeric carbons is in the β position.2082

OK, and so, it is tough because it is upside down; but it is in the equatorial position, right?--that is what we have, the β position.2091

Now, because this is a linear structure, that means it packs very tightly, and it ends up giving a rigid structure that is not soluble, because these pack so tightly, they want to stay with each other; they don't want to be surrounded by water molecules and disrupt those.2099

This is what is used in...is cellulose; these are cell walls; this is what nature uses in plant fibers to make rigid structures, and these are not digestible by most animals, and humans.2115

We can't eat wood or twigs and leaves--those kinds of things; and when we eat leaves, like lettuce or vegetables, the cellulose is something that passes through as insoluble fiber; so this is something that you can't digest.2130

That means we have a carboxylic acid, and on the α carbon, we have an amino group.2270

So, if we just say "amino acids," we are typically referring to α amino acids.2276

And amino acids are the building blocks to form proteins; so amino acids link together to form long polymers known as proteins.2281

If we take a look at their structure, their stereochemistry--so first of all, I have shown an example of an amino acid; if it is drawn this way, the side chain--this R group represents a side chain--it can be just hydrogen; one of the amino acids just has hydrogen here.2290

But we have a wide variety of groups that we can attach in this R position, and that is what gives us our different structures of amino acids, and kind of the building blocks to make different types of proteins.2310

There are about 20 naturally occurring amino acids, and that is kind of what we use as our alphabet to build all of these different words and sentences that we have as proteins.2322

This is an L-amino acid; L is the one that nature makes naturally.2333

The terms D and L are kind of historic on where those terms come from; so you don't necessarily need to know the background for that; but this is what the L form looks like.2341

The enantiomer, of course, would be the unnatural one--the one that we would have to make synthetically.2353

And, if we look at the stereochemistry here, if we were to look at that chiral center and assign it as an R or an S, it depends on what this R group is, of course, but almost all R groups...our #1 priority group is this nitrogen, because we are comparing nitrogen, carbon, and then this is usually carbon, and then a hydrogen.2361

So, this is usually 1; this is usually #2; this is usually #3; and the hydrogen is a dash; so if we go 1, 2, 3, what do we get there?--it looks like, counterclockwise, this is the S configuration.2385

And that is true for all amino acids except cystine: cystine--the R group is an SH, and this sulfur is a higher priority than this oxygen.2402

Because of that, those two, when we do the nomenclature--the position of 2 and 3 changes, and so we get the R configuration.2420

OK, so most naturally-occurring amino acids have the S configuration when we draw them out; you can draw them this way or this way or flip them up and down.2427

So sometimes the side chain is a wedge or a dash, depending on if I took this amino acid and just flipped it over; suddenly, it would still be naturally-occurring, but it would be a dash.2435

And we have an amine: now, carboxylic acids are acidic, and amines are basic; that means amines readily accept protons.2470

And so, the acid-base characteristics of amino acids and some of their side chains is really significant when we are looking at the structures of amino acids and proteins and so on.2481

And, in fact, if we look at a neutral pH like we would have in the blood (blood is not quite 7, but if we had something around 7), this carboxylic acid is acidic enough and this is basic enough that we will observe a proton transfer.2492

And so, instead of being written in the neutral form, really, amino acids should be written (if we are considering ones in solution and a physiological pH)...they should be drawn as a zwitterion.2511

So, you can always pick out an organic chemist when they go to draw an amino acid, because we just draw these nice neutral structures; but in almost every biochemistry textbook or biochemistry chapter, you are going to see it drawn as this.2530

Now, how do two amino acids come together to link together and eventually continue linking to make a polymer, to make a protein?2567

Well, it's a condensation reaction, and what happens is: the nitrogen of one amino acid acts as a nucleophile, and the carbonyl (right?--this is partially positive) of another acts as the electrophile.2576

And that is the reaction that we are going to have happen: so the nitrogen is going to come in and attack the carbonyl; it's going to do addition; it's going to do elimination.2593

I'm not going to show a complete mechanism here, but this is going to be our leaving group, and we are also going to lose one of these hydrogens; so the result (and again, I'm just going to leave the NH2 and the OH as neutral to make this discussion a little easier) is: we are going to form a (let me draw it up this way; we just kind of ended up flipping it over again--they end up getting flipped if we're drawing zigzags)...2602

This nitrogen has added into this carbonyl, and what functional group did we make?--we now have a carbonyl with a nitrogen group attached; this is called an amide.2634

We just formed an amide bond; and that is the key linkage that we have for proteins: we take the amine of one and the carboxylic acid of the other, and we make an amide.2646

And it is called a condensation reaction because, at the same time, we just lost a molecule of...what did we just lose here?--we lose this OH and this H; we lose a molecule of water.2662

We have amides when we are looking at proteins; amides are very stable functional groups; they are quite unreactive; so that means we can have all of these proteins that are pretty...can reliably resist hydrolysis and be quite stable, because the amide is such an unreactive functional group.2675

Now, another thing that is interesting--we call this the peptide bond; this amide bond that I just described is also called the peptide bond; and when we think about the stereochemistry, the conformations, the shape of a protein, an important part of that understanding is recognizing that what makes amides so stable is: there is resonance stabilization.2696

The nitrogen is very, very good at sharing its lone pair with the carbonyl.2721

And so, if we draw this resonance form, we have an O- now, and an N+.2726

OK, we have this resonance form; now think about resonance: remember, when we have resonance, that means it's not sometimes this and sometimes this; it is not an equilibrium.2746

It is not an equilibrium between these two structures; it means that the actual structure of the peptide bond, of this amide, is a blend--is a hybrid of those.2757

So, when we think about the hybridization of this nitrogen, it must be...if it's sp2 here, it must have been sp2 here as well.2767

Remember, resonance does not involve changes in bond angles or bond lengths--all of the atoms are frozen: we are just moving non-bonded and π electrons around; we are just moving electrons around in p orbitals.2779

OK, so that means the structure of this...and, of course, the carbonyl carbon is sp2 hybridized, still sp2 hybridized.2794

So, what we have is a trigonal planar nitrogen, trigonal planar carbon; so these four atoms, this nitrogen, this α carbon, these three atoms and these three atoms, are all coplanar.2801

And so, we can rotate in this position; we can rotate until, if this was another amide, that would be another planar chunk.2821

So you have these planes--these amide planar portions, and they can rotate, and then they will do that to have favorable interactions and so on.2830

When you are getting into protein structure, it is very important to realize the planarity of this amide bond, this peptide bond.2839

And an understanding of that comes from your foundations in organic chemistry, understanding resonance, understanding the stability of the amide, and in knowing how good the nitrogen is at donating its electron density.2849

In other words, it has a lot of this character--when you look at the hybrid, a lot of this character; and it's planar.2861

OK, so what are we going to do with proteins--how are those interesting to us?2870

Well, proteins are everything in the body: proteins are the work horse; they are what make all of the reactions happen.2873

Proteins are long polymers, so depending on their structure, they can be rigid; they can have strength; so when you look at the structure of muscles...2889

Now, this is something--growing up, when I learned about proteins, I knew that proteins--that amino acids built up proteins, and proteins are one of the things that we eat, and that one way you can get that is from meat, which is the muscle of animals.2899

So, I always knew that one thing you can build from proteins are muscles.2916

OK, but that is not the only thing: if you look at the structure of your skin, and rigid things like your bones, your hair, your nails, the material that makes your fingernails--those are all protein structures, as well.2922

So, we need proteins to build our bodies, to build all the different components of our body that make us be able to not just fall apart like a big mass of jelly.2936

They also act as enzymes in the reaction: an enzyme is something that catalyzes reactions.2951

If you think about all of the reactions that are going on in our body, that allow us to function--if you think about metabolism (you eat something and it gets broken down into various components and generates energy and so on), every one of those reactions is going to be catalyzed by something that allows the reaction to happen.2958

And it is going to be some kind of enzyme; so enzymes are the things that let the reactions happen.2980

We can have antibodies; so if you are sick, if you have something foreign coming in and your body needs to attack it, proteins are used to mount that defense.2985

It also helps in communication in your body, or transport; the hormones we have in our body, that monitor all of our levels; haemoglobin--the structure of haemoglobin (that is what transports the oxygen around our body in our red blood cells)--that is a protein, as well.2998

Proteins really get things done; in fact, they even do gene regulation.3017

Proteins are made from DNA, and the way that you turn on that DNA production or slow it down is: other proteins come in to do the signaling.3026

So, you could have signaling; you could have transportation; you could have structure--just a huge variety of actions that come from proteins.3037

At some point, you will probably need to be familiar with these or memorize these and get to know them.3055

We have certain amino acid side chains that are nonpolar; so we could just have a methyl group that is alanine; the isopropyl group is valine, I think--I really don't know my amino acids, so forgive me.3061

We can have some that are polar; so this one has an OH group; this one has an amide group on it; so we have some polar ones.3075

We have others that might be acidic themselves, so remember, these are attached to the amino acid; so all proteins have our one carboxylic acid and our one amino group.3083

In addition, part of the side chain, there can be a second carboxylic acid--something that is acidic--or maybe a phenol.3094

This is a carboxylic acid, so we know those are acidic; this is a phenol--phenols are also acidic.3101

It is very easy to lose this OH, because the resulting O-, the phenoxide, is resonance-stabilized; so phenols are acidic.3109

And we can also have functional groups that are basic; so again, in addition to the amine of the amino acid, you can have a second amine, and that could also serve as a base--and other rings, as well--other nitrogens.3116

OK, so our various side chains give different properties, because they have different reactivities, as well.3133

And we have a table here--one of many--again, you can Google this; any textbook will have it--organic or biochemistry textbook.3143

You can Google this, search online, find amino acid tables; and so, this is the one that just kind of shows...we have 21 amino acids being shown here.3152

And again, they are kind of broken up into ones that have charged side chains; so when we have basic side chains, they can get protonated and have a positive charge.3161

When we have acidic side chains, they can be deprotonated and have negative charges.3173

We have ones that will never have a charge--you know, alcohols won't react; amides won't react with anything.3178

And then, we have hydrophobic side chains--so just aromatic groups or alkyl groups, for example.3185

And so, depending on the properties of the functional group, your proteins are going to fold differently, are going to have a different shape, where we try and put these hydrophobic groups together and get them away from a polar solvent like water, and so on.3195

OK, so the actual structures of the amino acids are critical to their shape and their function.3215

Now, another property that you can learn about for amino acids is their isoelectric point--that is the pH at which the amino acid is going to be neutral--it's going to be zwitterionic.3224

It is still going to have charges, but overall, it is going to have a net charge of 0 for the majority of the molecules.3237

And so, for example, this is glycene, so glycene looks like it is missing its R group, its side chain; but actually, it just has a side chain of hydrogen.3243

Glycene is our simplest amino acid--it is not chiral, so this doesn't have D or L or R or S.3252

And so, we can look up the pKas in various tables; the pKa of the carboxylic acid of glycene is 2.35; the pKa of the ammonia group, of the amino group...3261

Now, when we say pKa, that is the tendency of something to donate a proton; so anytime we are talking about a pKa of an amine, we really mean the pKa of the ammonium group.3276

OK, so we are going to look at the protonated form of that amine when it has a positive charge, and we are asking, "How likely is that to lose its proton to go back to the neutral form?"3290

The pKa of a carboxylic acid starts at a neutral form and goes to an anion; the pKa of an amine starts at the protonated form and goes to the neutral structure.3300

OK, so sometimes textbooks or tables are not very clear on that; but you just want to make sure that you recognize that pKa is for the amino group.3310

These are kind of typical: acids are around 2; ammonium groups are around 10; and the pI is the pH at which it will be exactly neutral, or the majority of the molecules will be exactly neutral.3320

When we look at a pH around...let's look at a pH of 6, just so we're a little more precise (it would be about the same at 7, but a pH at 6): when this is at the isoelectric point, then we know we are going to have the zwitterionic form.3357

So, instead of the OH, this is...so pH of 6 means that my OH is going to be an O-, and my NH2 is going to be an NH3+.3375

Now, we are back to the zwitterionic form that...I said at the beginning that amino acids at neutral pH (or more technically, at their pI) are going to be zwitterionic like this.3387

Now, that means we have...anything that can be protonated will be, so you can think in base "anything that can be deprotonated will be," and at strongly acidic conditions "anything that can be protonated will be."3447

The amino group is going to stay protonated, but the carboxylic acid group, if you come down below 2.35, is going to get reprotonated, and now we are going to have a net +1 charge.3459

An amino acid can have a + charge; it can have a - charge; at the isoelectric point, it has a negative charge.3475

Now, what if our side chain also has an acidic or basic functional group?3485

OK, so for example, aspartic acid: we still have our amine; here is our amino acid; we still have the carboxylic acid and the amine group.3491

We always have those two pKas of the carboxylic acid and the ammonium; but it has second carboxylic acid group, so it has a third pKa, and that has a pKa of 3.86.3502

So again, pretty low--carboxylic acids are usually somewhere around 5 or so, or even lower, because we have a positively charged group here, so that makes it even more acidic.3518

Now, how do we calculate the pI there--at what pH is this molecule going to, overall, have a net charge of 0?3531

OK, well, what we do is: we take the two pKas that are closest in value, the two closest pKas--so this one is 2 and this one is about 4; those are much closer than this one out here at 9.8; so we are going to take those two closest pKas, and we are going to average those.3542

If we take 3.86 and 2.10, and we divide that by 2, we get 2.98, either exactly or close enough.3561

OK, so that is how we handle that; so in other words, we are asking, "When is this going to be neutral?"3571

Well, it has two acidic functional groups; so we are going to kind of ignore this high pKa and assume, "Well, no matter what, the ammonium group is going to be positively charged."3577

So, if the ammonium group is going to be positively charged, what we need to balance it out, to make it neutral, is: we need one negative charge.3591

And the way that we get one negative charge when we have two carboxylic acid functional groups is: we find the pKa that is exactly between those, where now half the molecules are going to have a negative charge.3599

And that will exactly average out to a -1 charge, instead of a -2 or a 0; it will average out to a -1; so our -1 cancels out the +1, and we have an overall neutral molecule: zwitterionic, but neutral.3610

OK, histidine is another example with a side chain that changes charge--can be charged.3628

Here is our amino acid; so this is the side chain now, and this group is what can be charged; it's this nitrogen here...I'm sorry, this nitrogen here--that can be basic, that can be protonated.3639

And so, it has a pKa of 6.10; now again, you might look at that and say, "Oh, that must be this hydrogen; we can deprotonate that hydrogen," but no: we are not going to remove the hydrogen that we added.3654

And amine works; its pKa is...it's the protonated version going back to the neutral nitrogen.3666

We would never want to form an N-; that is highly unstable, very, very reactive; so it's either an N+ or a neutral nitrogen.3672

So again, we think about it: we have these two basic side chains that can have positive charges or neutral; so when we are up at this pKa, the carboxylic acid is definitely going to be deprotonated.3701

Remember, the carboxylic acid gets deprotonated right away; it has a really low pKa.3714

So we already have one minus charge, one negative charge; so what we need to balance it out is one positive charge.3718

The way we calculate that pH is: we say, "Well, if we're right in between these two pKas, then we'll have one that is neutral and one that is positive, on average."3725

And so, we will have this +1 that cancels out the -1; we will have an overall neutral molecule; that is called the pI point, isoelectric point.3733

A lot of the work that you do with amino acids and proteins in biochemistry is to do titrations and study, with the amount of titrant that you have added, the amount of base that you added, what is the pH of the solution.3742

And so, from that, you can calculate what is the pKa of each functional group and things like what is the isoelectric point and so on.3761

Those are some of the calculations that you have in store, if you are headed to biochemistry.3769

This is a much more complicated case; let's ask, "What is the net charge?"--so this isn't so much an isoelectric point question--"What is the net charge of this tetrapeptide at pH of 6?"3776

This, again, is a common type of question that you have, that you should be able to evaluate and assess: for each functional group that is either acidic or basic, what will its state be?3789

Will it be in the protonated form, or will it be in the deprotonated form, based on the pH that is given?3803

OK, so first of all, let's look at this: this is the first tetrapeptide we have seen; that means we have four amino acids.3811

Let's start down here: here is our nitrogen, α carbon, carbonyl; so there is our peptide bond; there is our amide bond; there is one amino acid.3819

And it is polar, but it is not something that is going to act as an acid or a base.3889

OK, cystine has a pKa of 8; so this is actually acidic; an SH group is quite acidic, because it's reasonably easy to remove that hydrogen, because an S- with that large surface area delocalizes that charge over a large surface area; so that is a fairly stable negative charge.3894

OK, up here, this is called a guanidine functional group, and like most amines, it can be protonated; but rather than protonate down here, you could actually protonate this nitrogen (this is basic), because if I protonate here, you could have resonance stabilization to delocalize the charge.3919

And then, finally, we have glutamic acid; glutamic acid has an extra carboxylic acid functional group here, so of course, that is acidic.3959

We have all of these different groups; let's see how they are going to behave.3967

We have a pKa of 6, so that is slightly acidic; but still, we are close enough to 7 where we can assume--because I didn't give the pKas for these terminal groups, but we could assume, like any amino acid--we can assume that this carboxylic acid is a carboxylate, and this amino group is an ammonium.3970

So, we have an O- and an N+; we would expect that for those functional groups, any time we are in neutral pH.3997

I should also mention that the way we draw the amino acid--here are the abbreviations for glutamic acid, arginine, cystine, and asparagine; those are the 3-letter abbreviations for those amino acids.4004

And they are written out in this order--they are always written out in the order where this end has the nitrogen free; so this is described as the N-terminus (the N-terminal, the N-end--nitrogen end).4022

And we follow along to the amide, and then at the end, we have a carboxylic acid, and that is where our carbon is; so we call this the C-terminus.4037

We always have the N free amino group here, and then the N-group--that is the order in which we are writing it, so it's important, because it would be a different tetrapeptide if we had them in the opposite order.4047

That is important: I could never keep this straight, and I always thought it would just be nice if this was alphabetical, that the carbon end came first and the nitrogen end came last, because then that would be alphabetical.4062

But I guess, if you remember that it is not alphabetical--I guess it is just as easy to remember.4074

So, we're always starting with our N-terminus, and then we hook up an amide and an amide and an amide, and we end up with our carboxylate group at the end.4077

OK, so we will handle those; and then we look at our other functional groups, and here we have a carboxylic acid that has a pKa of 4.4085

So, you would have to be below that peak--that pH would have to be below that in order to be protonated.4096

Any pKa above that is basic, so we are going to deprotonate the carboxylate, just like we did over here.4102

OK, how about cystine?--cystine has a pKa of 8, so a pH of 6 means it's a lower pH, so that is an acidic medium; so is that going to be deprotonated?--there is not going to be anything to deprotonate this; this will still be protonated until we get above pKa of 8.4114

Amide, we said, is no reaction; so let's come back up to this guanidine functional group; this is basic, so this could have an N+; and a pH of 6...compared to pKa of 12, pH of 6 is much more acidic, so we have a good source of protons.4161

So, I think this is going to be protonated; it wouldn't become deprotonated until a very, very basic pH above 12.4177

Just like this free amine is protonated--you know what neutral pH is--then this guanidine is protonated, as well.4186

It ends up being neutral at this pH, with the particular functional groups that we have.4215

But in each case, you want to evaluate the amino acids separately and decide whether it's going to be negatively charged or neutral or positively charged.4220

OK, the next biomolecule we are going to look at are the nucleosides and nucleotides that make up DNA and RNA.4234

And the first thing we will look at are nucleic acids called ribonucleosides.4244

Now, ribo- tells us that we have a 5-carbon sugar; so that is part of this; and it is called a nucleoside when we take that 5-carbon sugar (here is 1, 2, 3, 4, 5) and, at the anomeric carbon, we attach a base--some kind of nitrogen structure.4250

And when we vary that base, we are going to get different ribonucleosides out.4275

And so, we have cytodine, which is abbreviated with the letter C; uradine for U; adenosine is A; and guanosine is G.4284

These ribonucleosides, C and U and A and G, are components, building blocks, that we are going to have for RNA.4294

Now, we call it a ribonucleotide, instead of a nucleoside, if on the 5' position, we add this phosphate group.4309

We describe it as phosphorylated ribonucleoside; so we start with a ribonucleoside, which just had an OH here, and we add this phosphate group, and now we call it a ribonucleotide.4324

So again, whatever base we have here, we could still have the A and the U and the G; but it's going to be called a nucleotide instead.4335

Now, the purpose of that phosphate is: this is now going to act as a linker, so that we connect one of these ribonucleosides to another.4344

We take these two ribonucleotides that have the phosphates on them, and same base, different base, whatever; and what we can do is: one of these oxygens at this position--at the 1, 2, 3 carbon--is going to add into the phosphorus and open up, and then collapse back down.4357

And we are going to get a linkage going on here; and we have this phosphate linkage.4383

This is the linker that we are going to use to connect the two sugars together.4391

So, kind of like we had with our proteins--we had a carbon terminus and a nitrogen terminus (C terminus and N terminus)--the ribonucleic acid structure (RNA) has a directionality to it, as well.4397

The end that has the free phosphate group we call the 5' end, because that is the linker that is on the 5 carbon; and the other end that has the free OH that is ready to attack another phosphorus group, and so on--we call that the 3' end.4417

So, it's a 5' end to a 3' end; and we are going to continue adding nucleotides, one by one, and we make this long polymer.4435

Now, we also have deoxyribonucleic acids; those start...we can look at the structure of deoxyribonucleosides, and these are the same structures we saw before, except notice that we are missing one of our OH's.4448

And so, this is no longer cytodine; it is deoxycytodine, deoxyadenosine, deoxyguanosine; so we still have C and A and G.4466

Now, we used to have uracil here, but instead, we have thymine...I'm sorry, it was uradine; now this is thymadine; and the difference here is that we have added a methyl.4476

So, if there is no CH3, then that is how we get the base that defines uradine; and here we have thymadine, and it's deoxythymadine, because there is no OH.4489

The four bases that we have--the four nucleic acids we have that go into DNA--are C and T and A and G.4501

They look a little different--the bases look a little different--for these two polymers.4511

OK, now, but they can still come together with the phosphate linkages to make chains, just like we saw for RNA.4518

Now, if you remember the structure of DNA--DNA has 2 of these strips, and they are linked together, and that is the helix that is going to be formed, the double-stranded helix.4525

Two of these strands are going to come together, and the way that they come together is by hydrogen bonding.4541

OK, and what is going to happen is: we are going to have one of the pyrimidine bases (so C or T--this 6-membered ring is described as a pyrimidine); it is going to link up with one of the purine bases (so this bicyclic base is called a purine).4546

And so, I'm just focusing on the base part, so we still have the sugar part and then the phosphate, and so that is kind of the backbone.4562

And what is going to happen is: when you have C and G lined up, we have the possibility for forming a hydrogen bond.4570

We form hydrogen bonds between hydrogens that are either on nitrogen or oxygen; those hydrogens are special, because they are very, very partial positive.4578

This NH bond is very polar--partial minus on the hydrogen, partial positive on that hydrogen; and so, that is going to interact; anything that has a lone pair of electrons can accept that hydrogen bond.4589

We call this a hydrogen bond donor; any NH or OH group is a hydrogen bond donor, and anything with a lone pair is a hydrogen bond acceptor.4606

And these structures are very nicely formed, because they are complementary in that we have a hydrogen bond donor lined up with a hydrogen bond acceptor, and then there is a second one we can form, because we have a lone pair here, and we have another NH.4623

We can form a second hydrogen bond, and guess what: we have another NH and another carbonyl, and we can have a third hydrogen bond.4642

So, these are just two molecules that fit together perfectly--very strong attraction to one another--and very reliably hold together.4650

OK, the same thing can go on with the T and A bases; OK, but here we have just two hydrogen bonds that can form between this carbonyl and hydrogen, and between this nitrogen and hydrogen.4663

OK, so in these cases, in DNA, they are all NH's that are the hydrogen bond donors; we don't have any alcohol groups--they are all NH's.4675

The hydrogen bond acceptors are either carbonyls or nitrogens with a lone pair.4688

What we end up with is this double-stranded structure; we have...here is the 3' end and the 5' end.4696

Remember, the backbone is--we have a ribose sugar, a deoxyribose sugar if it's DNA--deoxyribose sugar, and then this phosphate linker that connects at the anomeric carbon.4705

So, we have a sugar-phosphate backbone; we call it a sugar-phosphate backbone.4720

And attached to each of those sugars is one of the bases--either A or T or G or C.4730

And so, any time you have a C and an A and a T as the three bases in this portion of your DNA strand, then this is going to link up; it's going to be complemented by a G with three hydrogen bonds, and then a T with two hydrogen bonds, and another A with two hydrogen bonds.4738

And it is going to line up antiparallel--we call this antiparallel, because the 5' end of one (where the phosphate end is) is going to link up with the 3' end of the other.4756

We have the phosphate end on one end, and the phosphate end on a different end.4771

Now, when you take these two strands that are hooked together, it ends up twisting and coiling; we call this a double helix, or we just say it's a helix structure that we have.4780

The double helix structure is what Watson and Crick developed and came up with, and it was an extraordinary feat to elucidate this structure and figure out how DNA works.4792

And so, what we have here is this ribbon going along that back here (that is our sugar-phosphate backbone), and it is providing...kind of sticking out from that backbone are these bases that can link to bases on the other backbone.4806

This is a nice space-filling model; so here, we are showing...these are our bases that are linked together with the yellow and the red, or the blue and the green; those are in the middle, doing their hydrogen bonding.4846

When you look at the structure in a space-filling model, where we kind of see the space taken up by the electrons here, we see that the structure has major grooves--has large gaps, and has minor groups--has small gaps.4863

And that is interesting, because what can happen is: we can have small molecules come in and bind with the DNA at certain places; they usually bind in the major grooves, but sometimes they bind in the minor grooves.4880

This is called molecular recognition: remember, we have all of these side chains with all of their different properties and so on; and so, you could have a molecule come in and dock with just the right complementary natures and just the right...hydrophobic here, hydrophilic here, polar here, and so on; and they can kind of plug into the DNA.4893

That is...when you are ready to do a transcription of DNA, you have proteins that block in there and start to do the transcription process.4916

You can have therapeutic agents that can go lock in there to be an anti-cancer agent or something like that.4926

So really, this is when you are looking at the function of DNA--that structure is what allows it to do the things that it needs to do.4932

In DNA molecules, these are very, very long polymers, and they can be millions of DNA base pairs long; and, in fact, there are some cool at-home experiments you can do, where you isolate DNA strands.4941

If you go to YouTube, and you search for "isolate DNA from strawberries" or "bananas" (I think those are the two common ones), it talks about how you smash it up, and you put in some solvent.4956

You denature everything to kind of break apart...you need to break apart the cell walls to free the DNA.4967

And then, you can kind of go in there and pull it out and isolate it; and you can literally--they are so long, you can actually see the strands of these molecules; so it is really a very interesting experiment.4974

What do RNA and DNA--what function do they have?--how are they used by the body?4987

DNA, we know, is kind of like the blueprint that we have for what is going to tell the developing creature, "Are you going to be a cactus or a fish or a human?", right?4993

And the way that the DNA is used--those blueprints are read--is: first we have a process of transcription.5017

So, the DNA--the two strands separate, and RNA strands are formed; RNA, our single strand, forms.5023

They come in, and they form a complement to the single strand of DNA; we get RNA.5035

Transcription--when you transcribe something, you write it down--like, in a courtroom, you have a courtroom recorder who is taking notes; that is called a transcript, right?5040

It is when you have a recording of something; so we are transcribing the DNA, taking notes on what are the different nucleotides that are on there; and then, that RNA is used to synthesize proteins.5052

So, all the proteins that do the functions in our body--the way those proteins are made is from RNA.5068

That process is called translation; so just like you would translate something...if you are listening to something in Spanish and you want to translate it to English, you need to kind of look and say, "OK, you are saying these words; what does that mean?" and you do it in English.5076

So, it is then using that to translate: it is saying, "OK, here is your chunk of RNA; now what protein does that code for--what do I manufacture based on this code, the words that are there?"5092

And that is based on the genetic code; so we have done a tremendous amount in research in breaking down the code, deciphering the code.5109

And so, this is just a table; again, you can find a table like this in any Organic text or biochemistry text; or online, you can find them.5118

And this is showing, based on what the bases are, what the nucleotides are on your strand, what it translates to.5127

We look at 3 nucleotides at a time; that is called a codon; and depending on what those 3 letters are--what those three nucleotides are--it translates to a different protein.5142

When this is translated eventually, it is going to take a phenylalanine and attach it to the protein.5162

And then, it goes to say, "OK, who is my next amino acid that I should add on?"5171

And then, it looks at the next three letters; and if you have an A and a G and a U, that means you are going to build a serine.5176

And you can see that there is some redundancy built in--that there is not just one way to code for a serine.5183

And there are a lot of parts of DNA that are not used for coding proteins, and there is a lot of discussion on what is the purpose of those parts of the DNA.5190

There are so many mysteries still to solve, but it's amazing and fascinating how much has already been unraveled of the genetic code, when we take the genome.5200

The Human Genome Project looks at the entire genome of humans and deciphers it and tries to track it down.5210

Anyway, just a brief introduction into nucleic acids and how the organic molecules go to develop both DNA and RNA strands.5218

So finally, let's take a look at our last class of biomolecules, and that is lipids.5231

Lipids are triglycerides; you could also call them fats or oils--so things that are greasy.5235

Again, this is another part of our diet, fats--and a very important part of our diet, but hopefully not something that we have too much of, because our body doesn't handle that very well.5242

Let's take a look at the structure of fats and lipids from the chemistry point of view, and then see how they come together to function in the body (or in natural systems).5253

Here is the structure of glycerol: glycerol has 3 carbons, and it's a triol--1, 2, 3: propane triol.5263

And, if you take an alcohol, and you react it with fatty acids, we would call that--if we have a carboxylic acid with a really, really, really, really, really long carbon chain, we describe them as fatty, because they are hydrophobic.5271

We can either have saturated fatty acids, meaning there are no double bonds there--remember where we describe a π bond as a point of unsaturation...so if this is saturated with hydrogen (meaning it's just an alkane chain out here), we call that saturated.5285

And so, what is going to happen when you have an alcohol and a carboxylic acid?--you are going to replace the OH on the carbonyl.5305

We are going to have addition-elimination and replace the OH; so we are losing 3 molecules of water here, and we are going to form 3 esters; we are going to form a triester.5314

And so, this is described as a triglyceride; so when you are getting blood work done or something, your level of triglycerides is something they are measuring; that is measuring the level of lipids in your blood.5326

And we have fats (or oils, as we could describe them), and you have probably heard of saturated fats, monounsaturated fats, polyunsaturated fats...so that is simply describing how many double bonds, if any, are there in the lipid structure.5338

The difference between a saturated fat and an unsaturated fat is: if you have a saturated fat where these are all straight chains, those tend to pack very tightly together.5357

When you have molecules that pack very tightly together, they have high melting points; so a saturated fat will have a high melting point.5367

And so, something with a high melting point means, at room temperature, it is not going to be melted; it is going to be a solid; so these are solid fats.5379

What fats do we have that are solids at room temperature?--things like butter or animal fats, like lard, bacon grease--things that, at room temperature, are solids, are saturated fats.5386

When you have unsaturated fats--when you have double bonds--that causes a kink in the structure, and these molecules can no longer pack so tightly.5410

And if they don't pack so tightly, that means it is easier to get them to separate from one another and go into the liquid stage; and so, these are going to have lower melting points, and these are the fats that we know as liquids or oils at room temperature.5419

Things like canola...liquid oils are things like canola oil or olive oil, vegetable oils...right?...mineral oil; those are all things that must have points of unsaturation.5432

Now, liquid oils are healthier for you; saturated fats have some problems that aren't so heart-healthy, so that is why, in practice, it is a good idea to minimize our consumption of animal fats, of saturated fats, and stick to a diet that is high in monounsaturated or polyunsaturated fats.5453

So, the canola oil, olive oil--those are quite good to have in our diets.5477

OK, but it's hard to work with an oil; if you are baking, if you want to make a product--let's say you want to make an Oreo® cookie, and you want to have that nice cream in there; you can't do that with olive oil or canola oil.5481

It would just drip all over the place, right?--so you need a solid fat that is going to have the proper consistency; it also will have a longer shelf life.5493

These can kind of turn rancid; if you have an old bottle of vegetable oil and you open it up, you can smell, sometimes, a very bitter smell.5502

So, these are not entirely stable, and so that is why it's best to store them in the dark, and in cool temperatures, to minimize those reactions--because these π bonds can undergo reactions in air.5512

So a lot of times, for food manufacturers, they would take these liquid oils and do partial hydrogenation.5525

If you have ever read the ingredients of some crackers or cakes or something like that that you might buy at the store, one of the ingredients will be partially hydrogenated soybean oil, or something like that.5534

"Partially hydrogenated"--so that means they synthetically took this oil, which has some π bonds, and partially hydrogenated it; so that means they added hydrogen gas and some catalyst.5549

And what would that do to a π bond?--that would add H2 across the π bond and turn it into an alkane; if you get rid of some of the kinks in the structure, that makes it a solid structure.5560

Partially hydrogenated vegetable oil...things like Crisco oil or margarine--these are products that are man-made; they are vegetable-based, but they are solids.5571

And so, for a long time, we thought those were preferable to saturated fats, because we knew how bad saturated fats were; but then, it turns out that that chemical reaction not only hydrogenates some of the π bonds, but it also causes isomerization sometimes.5582

OK, the naturally occurring π bonds are going to have the cis conformation: the naturally occurring π bonds in lipids are cis.5601

And so, when you have that cis, when they are on the same side, that is when we get the bend in the chain, right?5616

It comes to one end, and then it goes back in the other; we get the bend, and that is how we get the lower melting point.5621

But sometimes, the catalyst can add onto the double bond, but not add the hydrogens; but the process of adding on and coming back off ends up isomerizing the π bond to make a trans double bond.5628

OK, and so, we call those trans fats; and quite recently, we have been learning that, actually, trans fats might be even worse for you than saturated fats.5642

So, it might be better to have bacon instead of margarine; there is a lot going on here.5652

But actually, the FDA has stepped in--the Food and Drug Administration has stepped in, saying that the nutrition labels that are on foods...that eventually, trans fats are going to also have to be labeled on there, because we know those are something to keep an eye out for.5657

I think there was a lawsuit that these trans fats kind of came to the public's attention; there was a lawsuit against Oreos®, saying that the stuffing in there was no good for you because of all of those trans fats.5672

And so, I think a lot of food science research has gone into finding just the right oils to use in there, that are healthy, yet stable, and have a good shelf life.5683

Using palm kernel oil or some naturally occurring oils that are solids is good.5694

The take-home message is: the more you can eliminate--minimize your fats, especially coming from processed foods, the better off you are going to be.5702

One of the things we can do is: we could do a saponification reaction.5716

And we call it a saponification because it actually is a way that you could make soap; so, in many parts of the world, in societies where they can't just go to a grocery store and buy detergents and soaps and shampoos and that kind of thing, those societies make their own soap.5720

And of course, historically, we would have to make our own soap if we wanted a cleaning agent.5739

The way that you make a soap is: you start with a triglyceride (so a triglyceride has, again, glycerol with these triesters), and you react it with water and base (like sodium hydroxide).5745

And what happens is: that base--that hydroxide--it does addition-elimination; we end up cleaving these ester bonds.5761

We eliminate a molecule of glycerol--we get back our glycerol--and these carboxylic acid groups get released as carboxylate salts.5768

We would protonate (this is written kind of funny--I'm sorry)...so this is an O- carboxylate salt, Na+; so we get the sodium salt here.5779

It would make the carboxylic acid; and then, of course, in a low pH, in base, that carboxylic acid would get deprotonated, and we would get the carboxylate salt instead.5789

And carboxylate salts act as soaps: if you take a structure like this and you put it in water, it kind of suds up and acts like a good cleaning agent.5800

OK, now, the question I have...or you could use Crisco, I think--we do an experiment at Cal Poly where you use Crisco shortening and cook it up with some base, and we get a soap solution.5855

Now, the question I had when I first read about this is, "Well, who in the world ever thought, 'You know what I'm going to use to make a soap solution?--I want to wash my clothes today: I'm going to start by putting in a bunch of lard, or some bacon grease or something--put it into my cooking pot with water; I'm going to take a handful of ashes out of this fire and throw it in there and mix it up, and somehow, that is going to make a good solution for me to clean my clothes."5867

But the theory goes: 100 years ago, when we have clothes that we make--we have clothes made out of cotton or something, they would get dirty after a while.5896

So, the women would want to wash them, so they would go down to the creek, or maybe make some kind of tub or make a little pool of water, and they would scrub their clothes and wash their clothes in the water--just using plain water.5906

Of course, you need to agitate it, and so maybe they would have a board that they could use--take a board and rub it, and use that to agitate it, like a washboard.5920

OK, and what the women would notice was that, if they had this little tub of water, as they continued to wash their clothes, let's say, over the course of the week, using this tub of water, the clothes would get easier and easier to get clean later in the week.5930

Scrubbing, scrubbing, scrubbing on Monday--but then, by Friday, you would do just a quick scrub, and your stain comes out.5948

And so, what was happening was: the animal fats--the greases and oils that were in their clothing, they were adding to the water; and the wood they were using to scrub was adding some of this base.5954

So, this is like our source of hydroxide; you get potash--it's actually potassium hydroxide, I think--the most common one.5976

The animal fats are the esters that we have, the triglycerides, so that would come from grease.5984

What they would notice was: they said, "Well, you know what, why don't I start on Monday just by adding in some bacon grease; and then, all of a sudden, I would have a great soap solution."5990

That is how, eventually, they got to this soap-making process, where they could make soap solutions; they could precipitate out the soap and make soap bars, and shave it up and make soap shampoo or flakes or something like that.6001

And so, to me, that is just a very interesting story on how we can make soap; an luckily, nowadays, we get to just run down to the grocery store, and we have a whole aisle full of cleaning agents that have wonderful dyes and perfumes that are in there, that make them smell good, and they work great.6015

And hopefully, they are good on the environment; that is something that, again, chemistry research continues to improve; and so on.6034

We get these carboxylate structures, and what is it that this RCO2-...why does that give us a soapy solution, and act as a soap?6049

If you take a look at the structure of the carboxylate salt (this is the O-, Na+), we have this hydrophilic head on it (hydrophilic because it's ionic), and then we have this long carbon chain, which is hydrophobic, because it's just an alkane or maybe an alkene, and certainly doesn't like water.6063

And, if you take this structure and you put it in water, what is going to happen is: it's going to cluster--it's going to congregate--in such a way to make a sphere that is coated on the outside with all of the ionic portions--the hydrophilic portions--and buried inside that sphere are all the hydrophobic portions--the long carbon chains.6086

So, this is described as a micelle; and all I have shown here is a cross-section; it looks very flat, but it's just kind of--it's a sphere.6109

In fact, if you have one of those toys--those little Koosh® balls that looks like all rubber bands--little rubber strings that are all tied together in a circle so it makes a big ball--that is kind of what a micelle looks like.6117

Now, water is all on the outside, interacting with the hydrophilic portion.6131

Now, does that act as a soap?--well, if you have a solution with these micelles in it, and you introduce some grease, and you agitate it (so you put it in a washing machine and it mixes, or you scrub it on a washboard, or with your hands), what is going to happen is: that grease is going to migrate; it's going to find its way into the center of the micelle, because grease...fats and oils are hydrophobic, and they are going to find their way into the hydrophobic interior of the micelle.6136

So now, it's going to be emulsified; it's going to be trapped in that micelle; and now, when I rinse my clothes with fresh water, the soap is going to get rinsed away, and it is going to take the grease with it.6167

Here is a really nice image of what a micelle looks like: so all on the outside here, we have the carboxylate groups.6179

Now, if you are looking at synthetic detergents and those sorts of things, instead of using carboxylate salts, they use other ionic parts to it; and so, that might lead to better cleaning action, better for the environment, less likely to precipitate out as soap scum--all sorts of different reasons that you want to change the molecular structure to this.6186

But, if you were making it the old-fashioned way, from saponification of an oil to make your own soap, then you are getting the carboxylate ionic part out here.6210

And then, inside, we have all of these very, very long hydrophobic chains.6221

And right in the middle there is where that grease is going to work its way in when we scrub, scrub, scrub our clothes.6227

That is why...how do we clean best?--we clean best when there is water and soap and agitation, because you want that grease to find its way into the micelles.6233

Another application that is kind of similar to the mechanism of saponification is the synthesis of biodiesel.6245

Now, what do we usually use as fuel for heating our home or to run our automobiles--that sort of thing?--we usually use petrochemicals; so we take crude oil; we refine that into its various boiling components; and we take the ones with a certain boiling point range (it's largely a mixture of alkanes), and that is what we use as liquid gasoline.6251

Now, the problem with that is: there is a finite amount of crude oil, and we don't always have access to that, and all sorts of problems.6277

So, if we can find alternate sources of carbon compounds that we can burn and use in our cars, then that would reduce our dependency on crude oil.6287

One option is to make what is known as biodiesel; so this is diesel--this is a fuel that is made from a biological source.6297

So, if we take a triglyceride (one of these lipids, fats, oils, something like that)--so for example, we use a lot of oil to cook French fries at our fast food restaurant--so we have all this used oil that is just garbage, that is going to be thrown out...6305

So, what if we could somehow take that oil and use that to power our cars?6320

OK, well, we can't just take the oil and dump it in there, because it is not flammable in that form, and it is viscous, and all sorts of other problems.6326

But we can convert it to biodiesel using a reaction that is very similar to the saponification reaction.6334

The reaction we do is: again, we start with a triglyceride--any triglyceride--and we react it with three equivalents of methanol and base.6340

Now, what is going to happen here...I should say, methoxide...you just...CH3...that is just a little easier way to see it...6350

You can imagine the methoxide adding in and then kicking out; so once again, we are going to be freeing up a molecule of glycerol.6359

And, at the same time, we are going to be making these methyl esters, because we are replacing...here are the ester groups that we are cleaving, and we are replacing the glycerol leaving group with a methoxy group that is coming in.6368

And so, these are described as fatty acid (there is our fatty carboxyl acid group) methyl esters, or FAME.6382

And this is something that could be used as biodiesel; this is another interesting reaction that you can do, and these esters are not soluble with the glycerol, so actually, as this...not saponification...it's actually a transesterification, because we are going from one ester to a new ester; so as this transesterification proceeds, the fatty acid methyl esters, the FAME components, are not soluble in the glycerol, because the glycerol is very polar and the others are quite nonpolar.6389

They actually separate out into two layers; and so you have a layer of your biodiesel and a layer that is glycerol, that could be repurchased for something else.6425

And so, you could take that biodiesel, and you could use it in certain automobiles.6436

Now, typically you need to have an engine that is manufactured to take diesel fuel--diesel fuel is a little different than the gasoline we use in most of our cars.6440

But it is interesting: I have seen a tractor running on biodiesel, and it smells like McDonald's French fries, because that was the kind of oil that they used.6451

Some of those volatile organic compounds are still around, so it sure smelled better than burning diesel or burning gasoline; that is for sure.6464

Now, a related biomolecule is called a phosphoglyceride; so this is now something that nature makes, and so, instead of a triglyceride, where we have three long-chain fatty esters, we have two long-chain esters and then this phosphate group.6475

So now, what we have is: we have built into one molecule--we have this ionic polar part and these long-chain nonpolar parts; so this is going to act just like the carboxylate salts that we saw, where they are going to congregate in such a way to minimize the hydrophobic or hydrophilic interactions.6494

OK, and one use for these--one way that those compounds aggregate is what is used in cell membranes, what is a component of cell membranes; and that is called a lipid bilayer.6522

These will congregate in such a way that all of the long carbon chains--the hydrophobic (right?--these are all hydrophobic)...they are all going to interact together, and all of the phosphate groups, the polar groups, are going to be...6538

So, instead of forming a micelle (which still could happen), this particular structure prefers to form a sheet, a layer; and then it is going to interact with a second layer, where the two hydrophobic regions align.6567

It is two layers of these phospho-glycosides; and what that gives us, then, is a membrane--is a big, long surface where water is happy on one side and it's happy on the other side, but it is not happy in the interior.6586

And what that gives us--what we have with the cell membrane--is: we have a barrier.6607

Things can't easily transport through there; we have to work to get something to go through, because it has to pass through this hydrophobic portion.6611

A few pictures: the bilayer acting as a barrier; this is a picture that shows some nonpolar molecules.6625

So, if you have some nonpolar--if you ingest some nonpolar molecules, they are going to find their way into the lipid bilayer, into the interior where all of the hydrophobic chains are.6632

And this is one theory of how certain anaesthetics work--things like ether fumes; if you take those in, you can lose consciousness.6643

And one of the ways that is theorized that that happens is: those molecules work their way into the bilayer, causing the cell membrane to expand; and then, the reaction to that is loss of consciousness.6657

And then, this is where we start to get...as soon as you start talking about lipid bilayers, now we are really starting to get into the world of biochemistry.6673

Now, what we care about, as an organic chemist, is this structure; now we are looking at the carbons and hydrogens and phosphoruses and so on; we have these long hydrophobic (I just saw a little typo there) carbon chains--two strands of those on the glycerol backbone.6681

And then, one of the phosphate groups--that is our hydrophilic head, the charged part.6701

And so, that is kind of just drawn in a cartoon as a head with two legs; and then, those will assemble to make something like this.6709

And then, that is the component of the cell membrane; and, when you actually look at the membrane of the cell, we have all sorts of things going on here--things that are embedded in it, things that prefer...like cholesterol is really hydrophobic, so that is going to be buried into the cell membrane at certain places.6725

Some things go across and through them; different proteins can be found there; etc.6743

And all of this is what we have when we just draw the picture of a cell with our cytoplasm and our nucleus and so on.6747

That perimeter that we draw on the outside is the cell membrane, and that is where we have these phospholipids coming together to form the bilayer.6755

This is starting to get biology and biochemistry-y enough for me to check out, so hopefully, this has given you a nice background into the various biomolecules that you will see down the road, that are significant in the functions of our bodies, and so on.6767

And hopefully, you have had enough organic chemistry background where the chemistry we talked about and the functional groups we talked about are things that made sense to you.6788

Thanks so much for joining me, and I hope to see you again really soon; have a great day.6796

Related Books

This is the actual book that Dr. Laurie Starkey teaches out of as a professor, and manages to be both clear and yet precise. The book presents a logical, systematic approach to understanding the principles of organic reactivity and the mechanisms of organic reactions.

This book includes all of the concepts typically covered in an organic chemistry textbook, but special emphasis is placed on skills development to support these concepts. This emphasis upon skills development will provide students with a greater opportunity to develop proficiency in the key skills necessary to succeed in organic chemistry.